Odegaard, Andrew

Abstract Purpose: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN. Experimental Design: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. Results: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. Conclusions: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions. Significance: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

Background: Cellular adhesion molecules (CAM) have a central role in the accumulation of circulating leukocytes at sites of vascular injury, infection and/ inflammation, and have been associated with the development of atherosclerotic plaque and coronary artery disease in mature adults. Objective: To test the hypothesis that higher overall circulating CAM levels in young adults predict cardiovascular disease (CVD) events over the next 18 years. Method: We measured several circulating CAM molecules (ICAM-1, P-selectin, E-selectin and VCAM) in the Coronary Artery Risk Development in Young Adults (CARDIA) study at exam year 7 (1992-93, black and white men and women, CVD-free, mean age 32, range 25-37 years, n=2428) and monitored incident CVD events (n=70, including coronary heart disease, stroke, and heart failure, adjudicated based on medical records) through exam year 25, mean age of 50 years. We ranked each CAM in quintiles (coded 0-4) and summed the ranks across CAMs into an index to examine the association with incident CVD with Cox regression models. Results: Unadjusted cumulative CVD event rates were 1.6% (sum of CAM quartile ranks 0-8: 22 events in 1353 participants), 2.3% (sum of ranks 9-12: 29/813), and 7.3% (sum of ranks 13-16: 19/262). In proportional hazards regression analysis adjusted for year 7 age, sex, race, clinic, education, smoking, diet, physical activity, body mass index, blood pressure, blood lipids, and blood glucose, sum of ranks 13-16 were associated with a higher risk of CVD compared to the referent (rank sum 0-8) (See Table). Conclusion: High levels of circulating CAMs at an early stage of adulthood (mean age 32, range 25-37 years) were associated with an increased risk of incident CVD events. CAMs may be an early biomarker for development of subclinical CVD, even in CVD-free young adults with low atherosclerosis burden and decades prior to the development of clinical CVD.