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PCSK9 variants not linked to sepsis risk

New data published in JAMA Network Open show that PCSK9 genetic variants were not associated with the risk for sepsis or sepsis outcomes in patients hospitalized with infection.

Of 10,922 white adults with infection who had genotypes available for PCSK9 functional variants seen at Vanderbilt University Medical Center (mean age, 60.1 years; 48.5% women), 3,391 developed sepsis, 835 developed cardiovascular failure and 366 died while in the hospital.

Analyses demonstrated no link between any of four functional PCSK9 variants — rs505151, rs11591147, rs11583680 and rs562556 — and sepsis, CV failure or in-hospital death with or without adjustment for age and sex or age, sex and comorbidities. In models adjusted for the latter, ORs for any loss-of-function variant were 0.96 (95% CI, 0.88-1.04) for sepsis, 1.05 (95% CI, 0.9-1.22) for CV failure and 0.89 (95% CI, 0.72-1.11) for death.

Similarly, in the full model adjusted for age, sex and comorbidities, a PCSK9 genetic risk score constructed by the researchers was not associated with sepsis (OR = 1.01; 95% CI, 0.96-1.06), CV failure (OR = 1.03; 95% CI, 0.95-1.12) and in-hospital death (OR = 1.05; 95% CI, 0.92-1.19). The genetic risk score was also not linked to the outcomes in any of the other models.

The researchers also found no association between PCSK9 expression and the studied outcomes, with ORs of 1.01 (95% CI, 0.95-1.06) for sepsis, 0.96 (95% CI, 0.88-1.05) for CV failure and 0.99 (95% CI, 0.87-1.14) for in-hospital death.

The study included data collected from 1993 to 2017 on white adults who had been admitted to Vanderbilt University Medical Center for infection and who had genome-wide genotyping available. Analyses occurred from 2018 to 2019. Only white patients were included in the study to “minimize the effects of population stratification on any association between genotype and outcomes,” according to the researchers.

“In this study, genetic variants of PCSK9 were not significantly associated with the risk of sepsis or with the outcomes of sepsis in patients hospitalized with infection. We believe that future studies should modify the algorithm used and include practice-based cohorts,” they wrote. – by Melissa Foster

Disclosures: Feng reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.