Dietary and other risk factors for cardiovascular disease analysed with Global Burden of Disease worldwide cohorts: lipid hypothesis versus fat-soluble vitamin hypothesis
Authors: Cundiff David K , Wu Chunyi 
Published: April 2021

AbstractBackgroundDebate about whether high intake of dietary saturated fatty acids (SFA) causes coronary heart disease (the lipid hypothesis) is ongoing.MethodsUsing worldwide Global Burden of Disease (GBD) data on cardiovascular disease deaths/100k/year, ages 15-69 years old in male and female cohorts (CVD) and dietary and other CVD risk factors, we formatted and population weighted data from 195 countries. The formatted rows of data (n=7846 cohorts) each represented about 1 million people, totaling about 7.8 billion people in 2020. We correlated CVD with dietary and other risk factors worldwide and in appropriate subsets. Outcome measures included CVD versus dietary and other risk factor correlations worldwide and in subsets.FindingsAfter empirical data exploration, we defined a “fat-soluble vitamin variable” Kcal/day (FSVV) as, “FSVV=processed meat + red meat + fish + milk + poultry + eggs + (SFA + polyunsaturated fatty acids (PUFA) + trans fatty acids (TFA)) * 0.46 (all in Kcal/day).” Low density lipoprotein cholesterol mmol/L correlated strongly positively with FSVV worldwide (r=0.780, 95% CI 0.771 to 0.788, p<0001, n=7846 cohorts), so we considered FSVV our marker variable to test both the lipid hypothesis and our fat-soluble vitamin hypothesis. LDL-C correlated negatively with CVD worldwide (r= -0.279, 95% CI -0.299 to -0.258, p<0.0001 as did FSVV versus CVD (r= -0.329, 95% CI -0.349 to -0.309, p<0.0001). However, FSVV correlated positively with CVD in the highest FSVV cohorts (mean male/female FSVV ≥567.27 Kcal/day: r=0.523, 95% CI 0.476 to 0.567, p<0001, n=974 cohorts).InterpretationSince FSVV correlated positively with CVD only in high FSVV cohorts, the data supported the lipid hypothesis only in GBD cohorts with high FSVV intake. Since both FSVV and LDL-C correlated negatively with CVD worldwide, only the fat-soluble vitamin hypothesis was supported worldwide. This GBD cohort data analysis methodology could be used to help develop food policy and education strategies for improving public health.FundingnoneResearch in contextEvidence before this studyRelating to dietary and other risk factors for early death from cardiovascular diseases worldwide, the EAT-Lancet Commission proposed the “Planetary Health Diet” to reduce non-communicable diseases and mitigate climate change. The Planetary Health Diet has been controversial and did not achieve the goal of leading a worldwide “Great Food Transformation” towards a more plant-based diet. The comparative risk assessment (CRA) systematic literature review-based methodology used in drafting the Planetary Health Diet has no significant competitors as published methodologies used to parse health effects of worldwide dietary and other risk factors. No consensus exists about an optimal range of diets for optimum human health, including cardiovascular disease prevention/treatment.Added value of this study□Cardiovascular disease deaths/100k/year in 15-69-year-old males and females (CVD) worldwide correlated with dietary risk factors had two patterns based on the amounts of kilocalories/day (Kcal/day) of animal foods and added fats. We differentiated the two patterns by defining a “fat-soluble vitamin variable” Kcal/day (FSVV=processed meat + red meat + fish + milk + poultry + eggs + (added saturated fatty acids (SFA)+polyunsaturated fatty acids (PUFA)+trans fatty acids (TFA)) * 0.46 (all in Kcal/day). Worldwide, all nine risk factors comprising FSVV correlated negatively with CVD, but in high FSVV cohorts (FSVV≥567.27 Kcal/day), all nine risk factors in the FSVV correlated positively with CVD.Implications of all the available evidenceAnimal foods and added fats afforded significant protection from CVD worldwide. The data suggested that the fat-soluble vitamins in animal foods and added fat facilitating gut absorption may have been partially or entirely responsible for the worldwide protection from CVD. However, in high FSVV intake cohorts, SFA in food and in extracted added fats facilitating atherosclerosis may have partially or entirely accounted for the positive correlation of FSVV and CVD. The findings suggest that a yet not precisely defined moderate amount of animal food and added fat intake contributed to lower cardiovascular risk relative to very high or very low intakes.