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Low-carbohydrate diets and prevalence, incidence and progression of coronary artery calcium in the Multi-Ethnic Study of Atherosclerosis (MESA)

  • Tian Hu (a1), David R. Jacobs (a1), Lydia A. Bazzano (a2), Alain G. Bertoni (a3) and Lyn M. Steffen (a1)...


The evidence linking low-carbohydrate diets (LCD) to CVD is controversial, and results from epidemiological studies are inconsistent. We aimed to assess the relationship between LCD patterns and coronary artery Ca (CAC) scores from computed tomography in the Multi-Ethnic Study of Atherosclerosis cohort. Our sample included 5614 men and women free of clinical CVD at baseline (2000–2002), who had a FFQ, a baseline measure and ≥1 measure of CAC during follow-up. We excluded those with implausible energy intake or daily physical activity. The overall, animal-based and plant-based LCD scores were calculated based on intakes of macronutrients. Relative risk regression and robust regression models were used to examine the cross-sectional and longitudinal relationship between LCD score quintile and CAC outcomes, after adjustment for multiple cardiovascular risk factors. The mean age of participants was 63 years. The median intakes of total carbohydrate, fat and protein were 53·7, 30·5 and 15·6 % energy/d, respectively. Among 2892 participants with zero CAC scores at baseline, 264 developed positive scores during 2·4-year follow-up (11–59 months). Among those with positive scores at baseline, the median increase in CAC was 47 units over the course of follow-up. The overall, the animal-based and the plant-based LCD scores were not associated with CAC prevalence, incidence and progression. In conclusion, diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.


Corresponding author

*Corresponding author: L. M. Steffen, fax +1 612 624 0315, email


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1. World Health Organization (2004) The Global Burden of Disease: 2004 Update. Geneva: World Health Organization.
2. Benjamin, EJ, Virani, SS, Callaway, CW, et al. (2018) Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 137, e67e492.
3. Grayburn, PA (2012) Interpreting the coronary-artery calcium score. N Engl J Med 366, 294296.
4. Detrano, R, Guerci, AD, Carr, JJ, et al. (2008) Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 358, 13361345.
5. Folsom, AR, Kronmal, RA, Detrano, RC, et al. (2008) Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 168, 13331339.
6. Agatston, AS, Janowitz, WR, Hildner, FJ, et al. (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15, 827832.
7. McClelland, RL, Chung, H, Detrano, R, et al. (2006) Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 113, 3037.
8. Yeboah, J, McClelland, RL, Polonsky, TS, et al. (2012) Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 308, 788795.
9. McClelland, RL, Bild, DE, Burke, GL, et al. (2008) Alcohol and coronary artery calcium prevalence, incidence, and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 88, 15931601.
10. DeFilippis, AP, Blaha, MJ, Ndumele, CE, et al. (2011) The association of Framingham and Reynolds risk scores with incidence and progression of coronary artery calcification in MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 58, 20762083.
11. Shea, MK, Booth, SL, Miller, ME, et al. (2013) Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr 98, 197208.
12. Eckel, RH, Jakicic, JM, Ard, JD, et al. (2014) 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129, Suppl. 2, S76S99.
13. World Health Organization (2003) Diet, Nutrition, and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation no. 916. Geneva: World Health Organization.
14. US Department of Health and Human Services and US Department of Agriculture (2015) 2015–2020 Dietary guidelines for Americans, 8th ed. (accessed April 2018).
15. Astrup, A, Meinert Larsen, T & Harper, A (2004) Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet 364, 897899.
16. Hu, T & Bazzano, LA (2014) The low-carbohydrate diet and cardiovascular risk factors: evidence from epidemiologic studies. Nutr Metab Cardiovasc Dis 24, 337343.
17. Hu, FB, Stampfer, MJ, Manson, JE, et al. (1997) Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337, 14911499.
18. Hooper, L, Summerbell, CD, Higgins, JP, et al. (2001) Dietary fat intake and prevention of cardiovascular disease: systematic review. BMJ 322, 757763.
19. Stein, K (2000) High-protein, low-carbohydrate diets: do they work? J Am Diet Assoc 100, 760761.
20. Bild, DE, Bluemke, DA, Burke, GL, et al. (2002) Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol 156, 871881.
21. Block, G, Woods, M, Potosky, A, et al. (1990) Validation of a self-administered diet history questionnaire using multiple diet records. J Clin Epidemiol 43, 13271335.
22. Willett, WC (2012) Nutritional Epidemiology, 3rd ed. New York: Oxford University Press.
23. Carr, JJ, Nelson, JC, Wong, ND, et al. (2005) Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. Radiology 234, 3543.
24. Detrano, RC, Anderson, M, Nelson, J, et al. (2005) Coronary calcium measurements: effect of CT scanner type and calcium measure on rescan reproducibility–MESA study. Radiology 236, 477484.
25. Nelson, JC, Kronmal, RA, Carr, JJ, et al. (2005) Measuring coronary calcium on CT images adjusted for attenuation differences. Radiology 235, 403414.
26. Ainsworth, BE, Irwin, ML, Addy, CL, et al. (1999) Moderate physical activity patterns of minority women: the Cross-Cultural Activity Participation Study. J Womens Health Gend Based Med 8, 805813.
27. Halton, TL, Willett, WC, Liu, S, et al. (2006) Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 355, 19912002.
28. Desquilbet, L & Mariotti, F (2010) Dose–response analyses using restricted cubic spline functions in public health research. Stat Med 29, 10371057.
29. Mansoor, N, Vinknes, KJ, Veierod, MB, et al. (2016) Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. Br J Nutr 115, 466479.
30. Mensink, RP, Zock, PL, Kester, AD, et al. (2003) Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77, 11461155.
31. Juraschek, SP, Miller, ER 3rd, Selvin, E, et al. (2016) Effect of type and amount of dietary carbohydrate on biomarkers of glucose homeostasis and C reactive protein in overweight or obese adults: results from the OmniCarb trial. BMJ Open Diabetes Res Care 4, e000276.
32. Selvin, E, Rawlings, AM, Lutsey, PL, et al. (2015) Fructosamine and glycated albumin and the risk of cardiovascular outcomes and death. Circulation 132, 269277.
33. Imamura, F, Micha, R, Wu, JH, et al. (2016) Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: a systematic review and meta-analysis of randomised controlled feeding trials. PLoS Med 13, e1002087.
34. Bueno, NB, de Melo, IS, de Oliveira, SL, et al. (2013) Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr 110, 11781187.
35. Hu, T, Mills, KT, Yao, L, et al. (2012) Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 176, Suppl. 7, S44S54.
36. Lagiou, P, Sandin, S, Lof, M, et al. (2012) Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. BMJ 344, e4026.
37. Mozaffarian, D, Rimm, EB & Herrington, DM (2004) Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr 80, 11751184.
38. Aune, D, Giovannucci, E, Boffetta, P, et al. (2017) Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose–response meta-analysis of prospective studies. Int J Epidemiol 46, 10291056.
39. de Oliveira Otto, MC, Mozaffarian, D, Kromhout, D, et al. (2012) Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr 96, 397404.
40. Praagman, J, Beulens, JW, Alssema, M, et al. (2016) The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr 103, 356365.
41. Appel, LJ, Moore, TJ, Obarzanek, E, et al. (1997) A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med 336, 11171124.
42. Estruch, R, Ros, E, Salas-Salvado, J, et al. (2018) Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 378, e34.
43. Pletcher, MJ, Tice, JA, Pignone, M, et al. (2004) Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 164, 12851292.
44. Tanenbaum, SR, Kondos, GT, Veselik, KE, et al. (1989) Detection of calcific deposits in coronary arteries by ultrafast computed tomography and correlation with angiography. Am J Cardiol 63, 870872.
45. Castelloe, J (2000) Sample size computations and power analysis with the SAS system. In Proceedings of the Twenty-Fifth Annual SAS Users Group International Conference, Paper 265-25, SAS Institute Inc.


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