Long Oral Presentation Nutrition Society of Australia 50th Annual Scientific Meeting 2026

Macronutrient Balance and Cardiovascular Disease Progression: A Compositional Multi-State Analysis in the 30-year Danish MONICA Cohort (146890)

Conghui Yang 1 2 , Alistair M Senior 1 2 , David Raubenheimer 1 2 , Stephen J Simpson 1 2 , Berit Lilienthal Heitmann 1 3 4
  1. Charles Perkins Centre, the University of Sydney, Camperdown, NEW SOUTH WALES, Australia
  2. School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia
  3. Section for General Practice, Department of Public Health, University of Copenhagen, Copenhagen K, Denmark
  4. Research Unit for Diet and Health, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

Cardiovascular disease (CVD) remains the leading cause of death worldwide, and diet is one of the most important modifiable determinants of cardiovascular health 1. Dietary protein, fat, and carbohydrate provide almost all dietary energy and have therefore been central to nutritional recommendations and cardiovascular research for decades. However, little is known about how the overall balance of dietary macronutrients influences CVD risk. This study aims to examine whether the relative composition of dietary protein, carbohydrate, and fat is associated with different stages of CVD progression. This prospective cohort study included participants from the Danish MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) study, followed from 1982 to 2012. Dietary macronutrient composition was analysed as a whole within the Nutritional Geometry Framework  2. Adjusted linear regression and Cox proportional hazards models examined associations with total energy intake, incident CVD, and mortality. Transition-specific Cox models within a multi-state framework evaluated associations across transitions between CVD-free, incident CVD morbidity, CVD mortality, and non-CVD mortality. Effect modification by age, sex, overweight/obesity, and metabolic disease was assessed. Among 1,851 participants, 509 developed incident CVD, 334 died from CVD, and 752 died from all causes during follow-up. A higher relative protein contribution was associated with higher CVD mortality (HR 1.81, 95% CI 1.04–3.14), whereas a higher relative carbohydrate contribution was associated with lower CVD mortality (HR 0.59, 95% CI 0.35–1.00). No statistically significant associations were observed for incident CVD or all-cause mortality. Multi-state analyses indicated that these associations were primarily driven by progression from incident CVD morbidity to CVD mortality, where a higher relative protein contribution was associated with increased risk (HR 2.22, 95% CI 1.04–4.73). Associations were stronger among men and participants with overweight. Among men, higher relative protein contribution was associated with higher CVD mortality following incident CVD morbidity (HR 4.64, 95% CI 1.30–16.29), whereas higher relative carbohydrate contribution was associated with lower risk (HR 0.37, 95% CI 0.14–0.96). Similar patterns were observed among participants with overweight (protein: HR 6.54, 95% CI 1.75–24.38, carbohydrate: HR 0.12, 95% CI 0.03–0.44). In conclusion, macronutrient balance may play a stronger role in CVD progression than CVD occurrence. These findings support a shift from single-nutrient thinking toward the balance of the whole diet and suggest that the period after a first cardiovascular event may be a particularly consequential window for dietary composition.

  1. Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol 2020;76(25):2982-3021. doi: 10.1016/j.jacc.2020.11.010
  2. Simpson SJ, Le Couteur DG, James DE, et al. The Geometric Framework for Nutrition as a tool in precision medicine. Nutr Healthy Aging 2017;4(3):217-26. doi: 10.3233/nha-170027 [published Online First: 20171207]