Subspecies of HDL associated with anthropometrical measures and physical activity

Associations of anthropometry and lifestyle factors with HDL subspecies according to apolipoprotein C-III

Literature - Koch M, Furtado JD, Jiang GZ, et al. - J Lipid Res. 2017, Epub ahead of print


Around 5-18% of HDL particles also contain apolipoprotein C-III (apoC-III) molecules, which are key regulators of triglyceride metabolism [1,2]. Low apoC-III levels are associated with a more beneficial lipid profile and less subclinical atherosclerosis [3]. Moreover, inhibition of apoC-III using antisense molecules resulted in less triglycerides and increased HDL-c [4].

Previous analyses of the Nurses’ Health Study and Health Professionals Follow-Up Study showed the importance of HDL subspecies, as HDL-c without apoC-III was negatively associated with increased risk of coronary heart disease (CHD), whereas HDL-c with apoC-III inversed this association [4,5].

Modification of apoC-III expression by, for example, lifestyle factors or anthropometrical measures, may be used for primary prevention. Current population-based study was performed to determine associations of HDL with and without apoC-III, with modifiable factors, including measures of waist and hip circumference, BMI and bioelectrical impedance derived fat mass, as well as lifestyle factors. In this study, 57,053 Danish-born residents were included, aged 50 to 65 years (1993-1997). All analyses were age- and sex-adjusted.

Main results

  • In men, around 9% of HDL particles carried apoC-III, which was 8% in women.
  • HDL without apoC-III levels were lower in overweight individuals and obese compared with normal weight individuals (% difference of -3.2 [95% CI -5.3 to -1.1] and -9.2 [95% CI -11.7 to -6.7], respectively). On the other hand, HDL containing apoC-III was 7% higher (95% CI 1.80-12.48) in obese individuals compared to normal weight individuals.
  • HDL containing apoC-III was also significantly higher when waist circumference, waist-to-hip ratio or body composition increased (2.8% per 15 cm [95% CI 0.36-5.30], 2.83% per 0.1 units [95% CI 0.26-5.46], 1.12% per 5 kg [95% CI 0.07-2.18], respectively) and HDL without apoC-III was significantly lower when these increased (-4.70% per 15 cm [95% CI -5.95 to -3.42], -3.93 per 0.1 units [95% CI -5.28 to -2.57], -2.15% per 5 kg [95% CI -2.71 to -1.58], respectively).
  • HDL containing apoC-III significantly decreased with 1% per 20 MET h/wk physical activity (95% CI -1.76 to -0.23), whereas HDL without apoC-III increased with 0.64% per 20 MET h/wk physical activity (95% CI 0.21-1.09).
  • These associations remained in multivariable models, though were attenuated and significance was lost for almost all associations with HDL containing apoC-III, which was mainly attributed to adjustment for physical activity.
  • Time spent on sport activities, biking or gardening did not associated with HDL subspecies, whereas less walking associated with statistically significant lower levels of HDL containing apoC-III levels and higher levels of HDL without apoC-III (quartile 4 -5.30% [95% CI -10.07 to -0.29] and 4.68% [95% CI 1.70-7.73], respectively).
  • There were no associations between smoking status or level of adherence to the Mediterranean diet and concentrations of HDL with and without apoC-III. Except that HDL containing apoC-III decreased with 0.92% per 1 gr legumes (95% CI -1.81 to -0.02) and HDL without apoC-III decreased with 0.50% per 0.1 unit of fat ratio only in the multivariable-adjusted model (95% CI -0.92 to -0.07), separate ingredients were not associated with HDL subspecies. In addition, HDL without apoC-III levels were 1.6% higher (95% CI 0.8-2.3) per 15 g/day more alcohol consumption, but this relation was not present for HDL containing apoC-III.


Several anthropometrical measures and physical activity strongly differentially associated with HDL subspecies, in which physical activity was the key factor. Regarding lifestyle, individuals with high alcohol consumption had higher levels of HDL without apoC-III. These factors are modifiable and it should therefore explored in intervention studies if an increase in physical activity differentially affects HDL subspecies via lowering abdominal obesity or by another mechanism. Furthermore, this study shows that beyond overall HDL, also protein composition of HDL might be relevant for the evaluation of primordial and primary prevention.


1. Jensen, M. K., E. B. Rimm, J. D. Furtado, and F. M. Sacks. 2012. Apolipoprotein C-III as a Potential Modulator of the Association Between HDL-Cholesterol and Incident Coronary Heart Disease. J Am Heart Assoc.1: jah3-e000232.

2. Mendivil, C. O., E. B. Rimm, J. Furtado, S. E. Chiuve, and F. M. Sacks. 2011. Low density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease. Circulation.124: 2065-2072.

3. Pollin, T. I., C. M. Damcott, H. Shen, S. H. Ott, J. Shelton, R. B. Horenstein, W. Post, J. C. McLenithan, L. F. Bielak, P. A. Peyser, B. D. Mitchell, M. Miller, J. R. O'Connell, and A. R. Shuldiner. 2008. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science.322: 1702-1705.

4. Gaudet, D., V. J. Alexander, B. F. Baker, D. Brisson, K. Tremblay, W. Singleton, R. S. Geary, S. G. Hughes, N. J. Viney, M. J. Graham, R. M. Crooke, J. L. Witztum, J. D. Brunzell, and J. J. Kastelein. 2015. Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. N Engl J Med.373: 438-447.

5. Di Angelantonio, E., N. Sarwar, P. Perry, S. Kaptoge, K. K. Ray, A. Thompson, A. M. Wood, S. Lewington, N. Sattar, C. J. Packard, R. Collins, S. G. Thompson, and J. Danesh. 2009. Major lipids, apolipoproteins, and risk of vascular disease. JAMA.302: 1993-2000.

Find this article online at J Lipid Res.

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