As described by Christel Kamani, MD, Geneva University Hospitals, Geneva, Switzerland, further blood analysis of participants in the Geneva Stairs Study [Meyer P et al. Eur J Cardiovasc Prev Rehab. 2010] has linked regular workplace physical activity in the form of stair climbing with decreased plasma level of proprotein convertase subtilisin/kexin type 9 (PCSK9). These results bolster the value of regular physical activity in the reduction of low-density lipoprotein cholesterol (LDL-C), suggesting a novel mechanism through the modulation of the PCSK9 pathway.

In the Geneva Stairs Study, 77 Geneva University Hospitals employees who were healthy but physically inactive regularly used stairs in their workplace instead of the elevator for a 6-month period. The use of stairs during the first 3 months was actively promoted, followed by another period of 3 months with no specific recommendations and where the use of stairs was less intensive. Monitoring over the 6 months revealed exercise-related improvements in a number of parameters usually associated with an increased risk of adverse cardiovascular events, including LDL-C (absolute change, −0.13% ± 0.49%; relative change, −3.0% ± 13.5%; P = .026). The findings implicated stair climbing as a simple means to reduce cardiovascular disease risk.

Presently, the blood samples from 67 of the study participants (mean age, 42.7 ± 8.8 years) were examined for PCSK9, a protein present in the liver as well as the kidney and tissues of the small intestine. PCSK9 functions to reduce the number of LDL receptors on the plasma surface of hepatocytes; thus, there is a correlation between plasma level of PCSK9 and plasma level of LDL-C.

In the first 3 months of the study, which was the period of peak stair-climbing activity, a significant decrease in PCSK9 levels was observed (baseline, 403.6 ± 166.0 ng/mL; 3 months, 324.3 ± 146.2 ng/mL; P = .001). In the final 3 months, when stair climbing was less intensive, serum PCSK9 levels rose to approximate the baseline condition (6 months, 381.8 ± 127.9 ng/mL; P = .260). A similar pattern was apparent for LDL-C, with a significant difference (P = .010) from baseline (3.5 ± 0.9 mmol/L) to 3 months (3.3 ± 0.9 mmol/L), with a return to the baseline value at 6 months (P = .527).

Plasma PCSK9 levels at baseline, 3 months, and 6 months are summarized in Figure 1.

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Figure 1.

Plot of Plasma PCSK9 Levels at Baseline, 3 Months, and 6 Months

PCSK9, proprotein convertase subtilisin/kexin type 9.

*P < .011 vs baseline; **P < .260.

Reproduced with permission from C Kamani, MD.

A multivariate analysis revealed a significant association of the decreased PCSK9 level at 3 months with physical activity intervention, after adjustment for age, baseline maximum oxygen consumption, plasma LDL-C value at baseline, plasma LDL-C value changes, and body mass index (Table 1).

In an analysis stratified according to the upper and lower baseline LDL-C values, the significant association between physical activity intervention and low plasma PCSK9 value at 3 months was similar across groups.

The findings are limited by the post hoc nature of the analyses, the lack of statistical power for some of the parameters, and the possible different influences of physical activity due to individual differences in the intensity of stair climbing.

Nonetheless, the findings indicate a novel means of cardioprotection via physical activity through the modulation of the PCSK9 pathway. Confirmation through a large randomized trial is needed.