Improved lifestyle led to increased PCSK9 levels in post-CABG men on statin treatment

Boyer M, Levesque V, Poirier P, et al.
Journal of Clinical Lipidology 2016;published online ahead of print

Background

Many coronary artery disease (CAD) patients are not in a good physical condition and have an elevated cardio-metabolic risk profile, including [1,2]:

• visceral fat accumulation, even within the normal BMI range
• elevated triglyceride, apoB, and apoA-I levels, as well as low HDL-c levels, despite statin treatment and target LDL-c levels.

Data suggest that CAD patients who change their lifestyle with physical exercise and an improved diet, achieve a reduction of their CVD risk [3,4]. However it is not clear whether lifestyle modification has an impact on PCSK9 levels in CAD patients on statin therapy. PCSK9 is involved in the regulation of cholesterol levels.

In this study, the impact of a 1-year lifestyle modification program on plasma lipoprotein and PCSK9 levels was assessed in 86 post-CABG (coronary artery bypass grafting) statin-treated men. Moreover, the association between plasma PCSK9 levels and markers of lipoprotein-lipid metabolism before and during the lifestyle intervention program was evaluated. The lifestyle modification program included a personalized healthy eating strategy and physical activity counselling (aim of weekly minimal 150 min. aerobic activity at moderate-to-vigorous intensity) and started at least 6 weeks after CABG.

Main results

No modifications were observed for total and LDL-c, or for apoB. However, lifestyle modification program did result in:

• mean reduction of visceral adipose tissue from 189.7 to 174.1 mL/5mm (P=0.04)
• mean increase of peakVO₂ from 24.9 to 28.6 mL O₂/min/kg (P<0.0001)
• mean reduction of VLDL-c from 0.62 to 0.55 mmol/L (P=0.0009)
• mean reduction of non-HDL-c from 2.23 to 2.13 mmol/L (P=0.04)
• mean reduction of triglycerides from 1.39 to 1.21 mmol/L (P=0.002)
• mean increase of apoA-I from 1.33 to 1.41 g/L (P<0.0001)
• mean increase of HDL-c from 1.17 to 1.31 mmol/L (P<0.0001)

The lifestyle modification program led to a rise of PCSK9 by 13.9 ng/mL (P 0.05). Changes in PCSK9 levels were not associated with changes in LDL-c or apoB levels, but were correlated with:

• increases in apoA-I levels (r=0.26; P=0.02)
• increases in fasting insulin levels (r=0.33; P=0.006)
• increases in HOMA-IR index (r=0.29; P=0.02)
• increases in peakVO₂ (r=0.23; P=0.05)
• changes in visceral adipose tissue (r=-0.23; P=0.04)
• changes in the ratio of total cholesterol/HDL-c (r=-0.23; P=0.03)

There were no statistical significant changes of PCSK9 levels upon changes in statin treatment.

Conclusion

In 86 post-CABG patients, increased physical activity and improved dietary habits had a modest positive influence on non-HDL-c, HDL-c, and triglyceride levels, but not on LDL-c and apoB. Moreover, PCSK9 levels were increased, which may explain the modest impact of a healthy lifestyle on atherogenic lipoproteins.

Find this article online at J Clin Lipidology

References

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2. Mora S,Wenger NK, Demicco DA, et al. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation. 2012;125:1979–1987.
3. O’Doherty MG, Cairns K, O’Neill V, et al. Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES). Eur J Epidemiol. 2016;31:455–468.
4. Safabakhsh L, Jahantigh M, Nosratzehi S, et al. The Effect of Health Promoting Programs on Patient’s Life Style After Coronary Artery Bypass Graft-Hospitalized in Shiraz Hospitals. Glob J Health Sci. 2015;8:48848.