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. 2020 Nov 3;19(1):187.
doi: 10.1186/s12933-020-01158-6.

Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance

C Macchi  1 , C Favero  2 , A Ceresa  3 , L Vigna  4 , D M Conti  4 , A C Pesatori  2 , G Racagni  1 , A Corsini  1   5 , N Ferri  6 , C R Sirtori  1 , M Buoli  3   7 , V Bollati  8 , M Ruscica  9
Affiliations

Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance

C Macchi et al. Cardiovasc Diabetol. .

Abstract

Background: Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk.

Results: In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9.

Conclusions: This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

Keywords: Beck Depression Inventory; Cardiovascular risk; Depression; Framingham risk score; Obesity; Proprotein Converatse Subtilisin/Kexin type 9.

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Conflict of interest statement

C Macchi, M Ruscica, A Ceresa, DM Conti, N Ferri, C Favero, L Vigna, AC Pesatori, G Racagni, CR Sirtori, V Bollati, M Buoli declare that there is no conflict of interest. A Corsini received honoraria from AstraZeneca, AMGEN, Sanofi, Recordati, Novartis, MSD, Mediolanum, DOC, Mylan and Pfizer.

Figures

Fig. 1
Fig. 1
Distribution of fasting plasma concentrations of PCSK9 levels (ng/mL; panel a) and HOMA-IR (panel b) in 389 individuals. Data are presented as histograms and box-plots. PCSK9 is normally distributed, whereas HOMA-IR shows a skewed distribution. PCSK9 pro-protein convertase subtilisin/kexin type 9, HOMA-IR homeostasis model assessment of insulin resistance. Min minimun, Max maximum, SD standard deviation
Fig. 2
Fig. 2
Scatterplots with regression line and confidence interval. Panel a—Association between severity of depression (BDI-II) and PCSK9. ∆ % represents the percentage increase in PCSK9 for one-unit increase in BDI-II score. Panel b–Association between PCSK9 and HOMA-IR on natural logarithmic scale, adjusted also for BDI-II. ∆ % represents the percentage increase in HOMA-IR for 100 ng/ml increase in PCSK9 concentration. Panel c—Association between severity of depression (BDI-II) and HOMA-IR on natural logarithmic scale. ∆ % represents the percentage increase in HOMA-IR for one-unit increase in BDI-II score. BDI Beck Depression Inventory, HOMA-IR homeostasis model assessment of insulin resistance, PCSK9 pro-protein convertase subtilisin/kexin type 9. Beta regression coefficients of panel a and b were used to estimate indirect effect of BDI-II on HOMA-IR
Fig. 3
Fig. 3
Conceptual diagram of causal mediation analysis, that hypothesized mechanism linking BDI-II and HOMA-IR. The solid black arrow represents the effect of BDI-II on HOMA-IR levels that operates directly or through a pathway different from the mediator analyzed in the current study (PCSK9). The dotted black arrows represent the suggested alternative pathway, where an indirect effect of BDI-II on HOMA-IR is mediated by PCSK9 levels. The black thin arrows indicate increased levels of HOMA-IR. BDI Beck Depression Inventory, HOMA-IR homeostasis model assessment of insulin resistance, PCSK9 pro-protein convertase subtilisin kexin type 9
See this image and copyright information in PMC

References

    1. Roth GA, Forouzanfar MH, Moran AE, Barber R, Nguyen G, Feigin VL, Naghavi M, Mensah GA, Murray CJ. Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med. 2015;372(14):1333–1341. doi: 10.1056/NEJMoa1406656. - DOI - PMC - PubMed
    1. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA et al: 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2019. - PubMed
    1. Khan SS, Ning H, Wilkins JT, Allen N, Carnethon M, Berry JD, Sweis RN, Lloyd-Jones DM. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2018;3(4):280–287. doi: 10.1001/jamacardio.2018.0022. - DOI - PMC - PubMed
    1. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur Heart J. 2014;35(21):1365–1372. doi: 10.1093/eurheartj/eht462. - DOI - PubMed
    1. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220–229. doi: 10.1001/archgenpsychiatry.2010.2. - DOI - PubMed

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