increased CV death

Ultra-Processed Foods Linked to Colorectal Cancer Risk, CV Death

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Making fresh foods available and affordable will promote public heath, editorialists say

A photo of three slices of previously frozen cooked pizza on a plate on a blue plaid tablecloth.

Regular consumption of ultra-processed foods was associated with an increased risk of colorectal cancer, all-cause mortality, and cardiovascular mortality, according to findings from two studies published in The BMJ.

In the first paper, which analyzed three prospective U.S. cohort studies, men in the highest quintile of consumption had a 29% higher risk of developing colorectal cancer compared with those in the lowest (HR 1.29, 95% CI 1.08-1.53, P=0.01), with an even greater association seen for distal colon cancer (HR 1.72, 95% CI 1.24-2.37, P<0.001), reported Fang Zhang, MD, of Tufts University in Boston, and colleagues.

These associations remained significant even after adjusting for BMI and nutritional quality indicators, they noted, and no association between ultra-processed food intake and colorectal cancer was seen among women.

In the second paper, which involved an Italian prospective study, an adjusted multivariable analysis showed a higher risk of all-cause mortality (HR 1.19, 95% CI 1.04-1.35) and cardiovascular mortality (HR 1.32, 95% CI 1.06-1.64) among adults in the highest quarter of the Food Standards Agency Nutrient Profiling System (FSAm-NPS) dietary index compared with the lowest quarter.

When looking at only those who fell within the two highest categories of ultra-processed food intake, based on the NOVA classification system, the associations remained for all-cause mortality (HR 1.19, 95% CI 1.05-1.36) and cardiovascular mortality (HR 1.27, 95% CI 1.02-1.58), reported Marialaura Bonaccio, PhD, of IRCCS Neuromed in Pozzilli, Italy, and colleagues.

In an accompanying editorial, Carlos Monteiro, MD, PhD, and Geoffrey Cannon, MA, both of the University of São Paulo in Brazil, noted that “the overall positive solution includes making supplies of fresh and minimally processed foods … available, attractive, and affordable. And sustaining national initiatives to promote and support freshly prepared meals made with fresh and minimally processed foods, using small amounts of processed culinary ingredients and processed foods.”

“Enacted, this will promote public health. It will also nourish families, society, economies, and the environment,” they added.

Colorectal Cancer

For their study, Zhang and colleagues used data on healthcare workers from three large U.S. prospective cohorts, including 46,341 men from the Health Professionals Follow-up Study from 1986-2014, 67,425 women from the Nurses’ Health Study I from 1986-2014, and 92,482 women from the Nurses’ Health Study II from 1991-2015. The NOVA classification system was used to assess levels of ultra-processed foods, and only physicians were blinded.

Over 24 to 28 years of follow-up, 3,216 cases of colorectal cancer were documented, 1,294 in men and 1,922 in women.

A higher consumption of meat/poultry/seafood-based ready-to-eat products was associated with an increased risk of colorectal cancer in men (HR 1.44, 95% CI 1.20-1.73), as was higher consumption of sugar-sweetened beverages (HR 1.21, 95% CI 1.01-1.44), while ready-to-eat or heat mixed dishes were linked to an increased risk for women (HR 1.17, 95% CI 1.01-1.36).

Interestingly, dairy-based desserts and yogurt were tied to a 17% lower risk of colorectal cancer among women (HR 0.83, 95% CI 0.71-0.97).

Potential explanations for the different patterns between the sexes might be due to the effects of obesity or sex hormones, Zhang and team noted.

They also acknowledged that the self-administered validated food frequency questionnaires used in the study included a limited list of pre-defined foods, which was a limitation to their study.

Cardiovascular/All-Cause Mortality

In the so-called Moli-sani study, Bonaccio and colleagues examined data on 22,895 participants (mean age 55, 52% women) in Molise, Italy from March 2005 to December 2010.

Over a median follow-up of 12.2 years, 2,205 participants died.

The authors jointly analyzed the the FSAm-NPS — used to derive the Nutri-Score front-of-pack label — and the NOVA classification system to assess mortality, finding that the magnitude of the relationship between the FSAm-NPS dietary index and all-cause mortality was attenuated by 22.3%, which was slightly higher than that for cardiovascular mortality (15.4% attenuated), while mortality risks linked to high ultra-processed food intake were not changed.

“So the problem with ultra-processed products has been suggested to be simply their poor nutrient profiles,” Monteiro and Cannon noted.

Study limitations included possible recall bias from self-reported dietary data, as well as possible social desirability bias, since ultra-processed food intake may have been underreported, Bonaccio and team said.

Very high HDL ‘red flag’ for all-cause, CV death risk in adults with CAD

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In adults with CAD, those with HDL of 80 mg/dL or greater are nearly twice as likely to die of any cause compared with those with HDL between 40 mg/dL and 60 mg/dL, according to an analysis of two large biobank databases.

In an analysis of data from nearly 20,000 patients, researchers also found the higher risk for all-cause and CV death associated with very high HDL, typically considered protective, was independent of traditional CV risk factors and alcohol use.

Graphical depiction of source quote presented in the article
Quyyumi is professor of medicine, director of the Emory Clinical Cardiovascular Research Institute and the Bruce Logue Chair for Cardiovascular Research at Emory University School of Medicine.

“Very high HDL levels are associated with increased risk for adverse outcomes, not lower risk, as previously thought,” Arshed A. Quyyumi, MD, FRCP, professor of medicine, director of the Emory Clinical Cardiovascular Research Institute and the Bruce Logue Chair for Cardiovascular Research at Emory University School of Medicine, told Healio. “This is true not only in the general population but also in people with known coronary artery disease. The higher risk with very high HDL levels is particularly seen in men, although women also have higher risk at very high HDL levels.”

Prospective biobank data

In a prospective study, Quyyumi and colleagues analyzed data from patients with confirmed CAD and high HDL, defined as at least 80 mg/dL, using UK Biobank (2006-present; n = 14,478; mean age, 62 years; 76.2% men) and Emory Cardiovascular Biobank (2003-present; n = 5,467; mean age, 64 years; 66.4% men) data. Patients without confirmed CAD were excluded. The primary outcome was all-cause death; secondary outcome was CV death.

The findings were published in JAMA Cardiology.

During a median follow-up of 8.9 years in the UK Biobank and 6.7 years in the Emory Cardiovascular Biobank, researchers observed a U-shaped association between HDL level, all-cause death and CV death, with higher risk among patients with low and very high HDL vs. patients with midrange values.

For the UK Biobank analysis, compared with patients with an HDL between 40 mg/dL and 60 mg/dL, patients with an HDL of at least 80 mg/dL were nearly twice as likely to die of any cause during follow-up, with a HR of 1.96 (95% CI, 1.42-2.71; P < .001) and 71% more likely to die of CV causes, with an HR of 1.71 (95% CI, 1.09-2.68; P = .02). Results persisted after adjustment for other CV risk factors, including hypertension, diabetes and smoking.

Findings were similar for patients in the Emory Cardiovascular Biobank, with findings for the UK Biobank persisting after further adjustment for genetic risk score.

In sensitivity analyses, all-cause death risk among patients from the UK Biobank with very high HDL was greater among men (HR = 2.63; 95% CI, 1.75-3.95; P < .001) compared with women (HR = 1.39; 95% CI, 0.82-2.35; P = .23).

“Physicians have to be cognizant of the fact that, at levels of HDL above 80 mg/dL, they must be more aggressive with risk reduction and not believe that that the patient is at ‘low risk’ because of high levels of ‘good cholesterol,’” Quyyumi told Healio. “We need to understand what the mechanisms underlying this increased risk are. What are the functional changes in HDL that lead to this higher risk?”

Very high HDL as ‘red flag’

Sadiya S. Khan

Gregg C. Fonarow

In a related editorial, Sadiya S. Khan, MD, MSc, assistant professor of preventive medicine (epidemiology) and medicine (cardiology) at Northwestern University Feinberg School of Medicine, and Gregg C. Fonarow, MD, FACC, FAHA, FHFSA, director of the Ahmanson-UCLA Cardiomyopathy Center, co-director of the UCLA Preventive Cardiology Program, co-chief of the division of cardiology at UCLA and the Eliot Corday Chair in Cardiovascular Medicine and Science, wrote that emerging data from healthy populations suggest a “paradoxical association” may be present, with higher mortality observed among people with very high HDL.

“Although the present findings may be related to residual confounding, high HDL-C levels should not automatically be assumed to be protective,” Khan and Fonarow wrote. “Clinicians should use HDL-C levels as a surrogate marker with very low and very high levels as a red flag to target for more intensive primary and secondary prevention, as the maxim for HDL-C as ‘good’ cholesterol only holds for HDL-C levels of 80 mg/dL or less.”

Previous analyses have suggested very high HDL may be a risk factor for all-cause death. As Healio previously reported, patients with HDL levels greater than 60 mg/dL in the Emory Cardiovascular Biobank had a nearly 50% increased risk for all-cause mortality, CV mortality and MI compared with those with HDL levels of 41 mg/dL to 60 mg/dL.

Reference:

Depression, stress tied to increased CV death risk in diabetes

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Elevated stress or depression may be linked to an increased risk for acute coronary heart disease or cardiovascular death among people with diabetes, according to results from the REGARDS study.

In the analysis, Doyle M. Cummings, PharmD, FCP, FCCP, of East Carolina University School of Medicine in North Carolina, and colleagues evaluated data from 22,003 adults (4,090 with diabetes; mean age, 64 years) from the REGARDS study. REGARDS is a population-based, prospective, longitudinal cohort study designed to evaluate factors associated with geographic and racial disparities in stroke incidence and mortality, with a particular focus on disproportionate stroke mortality in the southeastern U.S. (the “stroke belt”) in relation to the rest of the country.

In the current analysis, researchers compared the demographic, socioeconomic and CV risk traits of participants with and without diabetes in three categories: those with no comorbid depression and without elevated levels of self-reported stress, those reporting either depressive symptoms or elevated stress levels, and those reporting both depression and high levels of stress. The researchers then compared age-adjusted incidence rates for each type of CV event in participants with and without diabetes in the three categories.

The researchers found that participants with diabetes had a higher prevalence of elevated stress and/or depression (36.8%) compared with those without diabetes (29.5%; P < .001). Fully adjusted models revealed that in participants with diabetes, self-reported depression or elevated stress was associated with a significantly higher incidence of stroke and CV death. This increased incidence was not seen in participants without diabetes.

In participants with diabetes, the existence of one of the behavioral comorbidities increased the risk for CV death by 53% in relation to participants with diabetes without behavioral comorbidities. The presence of both behavioral comorbidities in participants with diabetes increased the risk for CV mortality by 115% in relation to patients with neither depression nor elevated stress, even after adjustment for various demographic and CV risk factors.

Although participants without diabetes but with one or both behavioral comorbidities also showed a trend toward increased risk for CV death compared with neither comorbidity, these increases were much smaller (12% for one and 27% for both) and did not reach statistical significance.

“These findings demonstrate the persistent disparities and negative CV impact of these comorbidities at the population level and suggest the need for more careful integration of behavioral screening and management in primary care settings, where most patients with type 2 diabetes are managed,” the researchers wrote.