| Title: | LDL lowering effect of PCSK9 inhibition is reduced in women |
| Journal: | European Heart Journal - Cardiovascular Pharmacotherapy |
| Published: | 20 Feb 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36722156/ |
| DOI: | https://doi.org/10.1093/ehjcvp/pvad009 |
| URL: | https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvad009/49273261/pvad009.pdf |
Publication 11111
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Abstract
AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels.</p>
METHODS AND RESULTS: We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P < 0.0001, women = 175 mg/dL vs. men = 152 mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD = 7.6 mg/dL, 95% confidence interval: 2.7-12.4, P = 0.002) than in women.We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: -35 mg/dL vs. -26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e-04).</p>
CONCLUSION: These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.</p>
7 Authors
- Veronika A Myasoedova
- Antoine Rimbert
- Marina Camera
- Cedric Le May
- Romain Capoulade
- Bertrand Cariou
- Paolo Poggio
1 Application
| Application ID | Title |
|---|---|
| 49823 | Genetic predisposition to cardiovascular and metabolic diseases |
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