The Carbohydrate Controversy

A healthy diet is considered one of the pillars of cardiovascular disease prevention. Multiple specialty groups provide nutrition recommendations in cardiovascular disease prevention guidelines.^1,2 Diets containing low amounts of carbohydrates have gained popularity due in part to beneficial effects on weight loss compared with low-fat diets.³ However, the role of carbohydrates in cardiovascular disease prevention is not well established, as the risk of death appears to be higher at both extremes of low and high levels of carbohydrate intake.⁴ A potential explanation for these findings involves carbohydrate quality such that greater intake of certain carbohydrates, like fruits, vegetables, and legumes, are associated with lower risk of mortality.⁵ There are several markers of carbohydrate quality but the association of each measure with cardiovascular disease risk is not well established.⁶

Are All Carbohydrates Created Equal?

Carbohydrates are one of the major classes of nutrients and include sugars, starches, and fibers. High-fiber and whole-grain foods are considered beneficial for cardiovascular disease prevention.⁶ Recent studies have examined the associations of glycemic index and glycemic load, indicators of carbohydrate quality, with risk of cardiovascular disease events.^7,8 Glycemic index is a measure of how much dietary carbohydrates increase blood glucose levels. Carbohydrates that cause a spike in blood glucose, like sugar-sweetened beverages, have a high glycemic index compared with those that lead to a less pronounced rise in glucose, such as legumes. While glycemic index does not account for the amount of carbohydrate intake, glycemic load is the product of glycemic index and total available carbohydrate content in a given amount of food.

Glycemic Index, Glycemic Load, and Cardiovascular Disease
Randomized clinical trials of low glycemic index and low glycemic load interventions demonstrated improvements in cardiometabolic factors.^9,10 Observational studies have yielded mixed results regarding the association of glycemic index, glycemic load, and adverse events.^6,8 Furthermore, prior studies examining dietary patterns and cardiovascular disease risk focused on individuals from North America and Europe with less known about those from non-Western regions.

In a recent analysis, Jenkins, et al. examined the association of glycemic index and glycemic load with risk of cardiovascular disease among adults enrolled in the Prospective Urban Rural Epidemiology (PURE) study.⁷ The PURE study was a prospective cohort study that evaluated dietary patterns among individuals aged 35-70 years from high-, middle-, and low-income countries across the world. The glycemic index was estimated for participants based on country-specific diet questionnaires and glycemic index values for multiple carbohydrate categories. Glycemic load was determined based on the glycemic index and total carbohydrate intake. The primary composite outcome was all-cause death or a cardiovascular disease event, including cardiovascular death, nonfatal myocardial infarction, stroke, or heart failure.

The dietary patterns of 137,851 participants across five continents from the PURE study varied widely with the highest glycemic index observed in China and greatest glycemic load in South Asia. Over 9.5 years of follow-up, 14,075 participants had a primary outcome event. After adjusting for demographics, socioeconomic and cardiovascular disease risk factors, participants in the highest glycemic index quintile had higher risk of death or cardiovascular disease compared with those in the lowest quintile (hazard ratio [HR], 1.25; 95% CI, 1.15 to 1.37). These findings were consistent among participants with (HR for quintile 5 vs. 1, 1.51; 95% CI 1.25 to 1.82) and without established cardiovascular disease (HR for quintile 5 vs. 1, 1.21; 95% CI 1.11 to 1.34). In contrast, the association between greater glycemic load and higher risk of death or cardiovascular disease was only observed in the secondary prevention cohort (HR for quintile 5 vs. 1, 1.34; 95% CI, 1.08 to 1.67).

This analysis from the PURE study suggests that higher glycemic index and glycemic load are associated with greater risk of adverse cardiovascular disease events in adults with established cardiovascular disease. However, this study is limited by its observational study design. Measures of carbohydrate quality were determined based on questionnaires which are subject to recall bias. Furthermore, despite adjustment for several factors, residual confounding cannot be excluded.

Conclusions and Future Directions

Glycemic index and glycemic load represent markers of carbohydrate quality with prognostic implications for cardiovascular disease. Understanding the quality of carbohydrate intake, based on glycemic index and glycemic load, may help identify dietary intake patterns associated with risk of cardiovascular disease. Future randomized controlled trials are needed to evaluate the cardiovascular effects of low glycemic index diets.

References

1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;74:e177-e232.
2. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315-81.
3. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008;359:229-41.
4. Seidelmann SB, Claggett B, Cheng S, et al. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health 2018;3:e419-e428.
5. Miller V, Mente A, Dehghan M, et al. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study. Lancet 2017;390:2037-49.
6. Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet 2019;393:434-45.
7. Jenkins DJA, Dehghan M, Mente A, et al. Glycemic index, glycemic load, and cardiovascular disease and mortality. N Engl J Med 2021;384:1312-22.
8. Shahdadian F, Saneei P, Milajerdi A, Esmaillzadeh A. Dietary glycemic index, glycemic load, and risk of mortality from all causes and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies. Am J Clin Nutr 2019;110:921-37.
9. Jenkins DJA, Kendall CWC, McKeown-Eyssen G, et al. Effect of a low–glycemic index or a high–cereal fiber diet on type 2 diabetes: a randomized trial. JAMA 2008;300:2742-53.
10. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial. JAMA 2007;297:2092-102.

Clinical Topics: Anticoagulation Management, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Diet

Keywords: Metabolic Syndrome, Diabetes Mellitus, Blood Glucose, Prospective Studies, Glycemic Index, Dietary Carbohydrates, Cardiovascular Diseases, Glucose, Diet, Fat-Restricted, Weight Loss, Fabaceae, Prognosis, Secondary Prevention, Follow-Up Studies, Factor X, Cohort Studies, Food, Heart Failure, Myocardial Infarction, Risk Factors, Socioeconomic Factors, Socioeconomic Factors, Demography, Stroke

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