Contribution of cardio-vascular risk factors to depressive status in the PREDIMED-PLUS Trial. A cross-sectional and a 2-year longitudinal study

PLoS One. 2022 Apr 13;17(4):e0265079. doi: 10.1371/journal.pone.0265079. eCollection 2022.


Background: Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial.

Methods and findings: Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol <160 mg/mL showed higher odds of depression than LR [OR (95% CI) = 1.77 (1.13, 2.77) and 2.83 (1.25, 6.42) respectively)] but those with total cholesterol ≥280 mg/mL showed lower odds of depression than LR [OR (95% CI) = 0.26 (0.07, 0.98) and 0.23 (0.05, 0.95), respectively]. All participants decreased their BDI-II score after 2 years, being the decrease smaller in MR and HR diabetic compared to LR [adjusted mean±SE = -0.52±0.20, -0.41±0.27 and -1.25±0.31 respectively). MR and HR participants with total cholesterol between 240-279 mg/mL showed greater decreases in the BDI-II score compared to LR (adjusted mean±SE = -0.83±0.37, -0.77±0.64 and 0.97±0.52 respectively).

Conclusions: Improving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response. International Standard Randomized Controlled Trial (ISRCTN89898870).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholesterol
  • Cross-Sectional Studies
  • Depression* / epidemiology
  • Diabetes Mellitus / epidemiology
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Longitudinal Studies
  • Male
  • Metabolic Syndrome / epidemiology
  • Middle Aged
  • Randomized Controlled Trials as Topic


  • Cholesterol

Associated data

  • ISRCTN/ISRCTN89898870

Grant support

The PREDIMED-Plus trial was supported by the European Research Council through a grant to MAM (Advanced Research Grant 2013-2018; 340918). The project was also supported by the official funding agency for biomedical research of the Spanish Government (ISCIII) through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects),who awarded grants to JS and JV (PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732 and PI17/00926). The International Nut&Dried Fruit Council- FESNAD also provided funding through a grant to MAM (201302), and Recercaixa also awarded a grant to JS (2013ACUP00194). The Department of Health, Generalitat de Cataluña by the calls “Acció instrumental de programes de recerca orientats en làmbit de la recercaila innovació en salut” and “Pla estrategic de recerca i innovació en salut (PERIS),” also awarded a grant to FF (SLT006/17/00246). This research was also partially funded by: Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); Generalitat Valenciana (PROMETEO/2017/017); SEMERGEN, CIBEROBN, FEDER and ISCIII (CB06/03); EU-H2020 Grants (Eat2beNICE/h2020-sfs-2016-2, ref.728018; PRIME/h2020-SC1-BHC-2018-2020, ref: 847879). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the funding sources took part in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication.